EP0005849B2 - Process for preparing alpha-chloro-n-monoalkyl-acetoacetamides - Google Patents

Description

a-Chloro-N-monoalkyl-acetoacetamides are valuable intermediates for the production of insecticides based on phosphoric acid esters, in particular dialkyl phosphates of N-monoalkyl-3-hydroxycrotonic acid amide (cf. US Pat. No. 2,802,855).

The a-chloroacetoacetamides have hitherto been produced by chlorination of the corresponding acetoacetamides, considerable amounts of the a, a-dichloro-acetoacetamides being formed as by-products, but their separation is practically impossible because of similar physical properties. Several processes have therefore become known which lead to practically pure α-chloroacetoacetamides by subsequent selective dehalogenation of the α, α-dichloroacetoacetamides. However, such methods require additional measures and are therefore uneconomically expensive.

After the process described in DE-PS 1493022 (which corresponds to US Pat. No. 3,449,421), which is restricted to the production of a-chloro-N, N-dialkylacetoacetamides, the chlorination of the N, N-dialkylacetoacetamides with hypochlorous acid can , N-chlorourea and / or tert. Butyl hypochlorite can be carried out at temperatures from 0 ° C to 80 ° C. Water is recommended as a suitable solvent, especially if hypochlorous acid, which can be prepared in situ by the reaction of chlorine with water, is used as the chlorinating agent. Since the reaction in the lower temperature range is too slow, the process is advantageously carried out at room temperature and above, the selectivity being improved by the use of urea. As can be seen from Example 2, 96.4% of a-chloro-N, N-dimethyl-acetoacetamide in addition to 0.6% of a, a-dichloro-N, N-dimethylacetoacetamide and 1.1% of NN- Obtained dimethylacetoacetamide (unreacted starting material), which corresponds to a conversion of 92.6%.

However, the transfer of this process to the production of a-chloro-N-monalkylacetoacetamides, such as a-chloro-N-methyl-acetoacetamide, was not possible without the formation of large amounts of the corresponding a, a-dichloro-N-methyl-acetoacetamide. From DE-PS 1 618 207 (which corresponds to US Pat. No. 3,483,252) a method has therefore become known by which N-monoalkylacetoacetamides are used at temperatures below 0 ° C., that is, in the range from -8 ° C. to - 25 ° C are chlorinated in the presence of water and urea and the presence of an alcohol is additionally required. As can be seen from Example 1, 90% of a-chloro-N-methylacetoacetamide in addition to 5% of a, a-dichloro-N-methylacetoacetamide and 1.6% of unreacted starting material are obtained under these conditions.

However, even this process was unsatisfactory when it was transferred to the large-scale sector, since the amount of a, a-dichloro compounds formed as undesired by-products is still too great and the large amounts of urea required (0.5 mol per mole of chlorine used) are in are highly uneconomical.

However, according to the process described in DE-OS 2049045 (which corresponds to NL application 7014636), it should be possible to chlorinate both N-monoalkyl and N, N-dialkylacetoacetamides at temperatures below 0 ° C. without addition of urea, if an alkanol with 1 to 6 carbon atoms is used as solvent, which optionally contains 5 to 40% water, preferably about 15 to 20% water. The selectivity of this process with respect to the formation of the desired a-monochloro derivatives is said to be increased compared to the previously known processes, since only about 5% of the a, a-dichloro derivatives are formed, which if necessary after removal of the alkanol in a known manner by treatment with a Reductants can be selectively dehalogenated. As can be seen from the examples, which deal exclusively with the chlorination of N-monomethylacetoacetamide, the best results in terms of conversion and selectivity were achieved with ethanol as the solvent, which contained 7.4% of water. However, an increase in the water content to 50% or even 75%, under otherwise almost identical conditions, resulted in a significant decrease in turnover and selectivity. This DE-OS therefore conveys the teaching that the chlorination of acetoacetamides, in particular of N-monomethylacetoacetamide, only in dilution with an alkanol, the water content of which must not exceed 20%, at temperatures below -15 ° C. to form the corresponding a-monochloro derivatives with a conversion of over 95% and a selectivity of the same order of magnitude in acceptable reaction times, that is, can be carried out within about 2 hours. Any change in these reaction conditions, in particular an increase in the water content in the specified solvent, is associated with a reduction in the conversion and / or the selectivity, it being expressly pointed out that the reaction time also increases with increasing water content. The application of this method is therefore limited in practice. In addition, additional measures for removing the alkanol by distillation are required before the reaction product can be worked up in a known manner.

These narrow limits have obviously been recognized by the applicant itself, as can be seen from the state of the art in US Pat. No. 3,917,694, which indicates that in this process, turnover and selectivity tend to decrease in many cases when the reaction is carried out on an enlarged scale. In this US-PS therefore modifies the process for the chlorination of N-alkyl- or N, N-dialkylacetoacetamides at temperatures below 0 ° C. and an alkanol as solvent by limiting the rate of chlorine introduction at the beginning and increasing progressively as the reaction proceeds. This is intended to achieve a constant high conversion and selectivity. As can be seen from the examples, however, good results are only achieved in the chlorination of N-monomethylacetoacetamide if urea is used at the same time, namely in amounts of up to 1 mol per mole of N-monomethylacetoacetamide used, the name of which is called the “chlorination catalyst” this large amount is no longer justified.

These known processes prove that the chlorination of acetoacetamides with chlorine can have a positive influence on the selectivity with regard to the desired formation of the corresponding monochloro compounds by lowering the reaction temperature, selecting the solvent and / or slowing down the rate of chlorine introduction. Achieving high selectivity, however, only makes sense in practice if it does not have to be purchased at the expense of incomplete implementation. However, high selectivity combined with high conversion can be achieved by the processes known hitherto, in particular in the chlorination of N-monoalkylacetoacetamides, which are more sensitive than the corresponding N, N-dialkylacetoacetamides with regard to the undesired formation of alpha, alpha-dichloro compounds , can only be achieved through elaborate measures.

worin R, Alkylrest mit 1 bis 3 C-Atomen bedeutet, durch Umsetzung von N-Monoalkyl-acetoacetamiden der allgemeinen Formel

worin R, die angegebene Bedeutung hat, mit Chlor in Gegenwart von Wasser enthaltenden Lösungsmitteln bei Temperaturen unter 0°C zur Verfügung zu stellen, das bei einem Umsatz von mindestens 95% eine hohe Selektivität von mindestens 97% gewährleistet, ohne dass hierzu aufwendige Massnahmen, wie die Einschaltung einer zusätzlichen Destillationsstufe zur Entfernung von Lösungsmittel, der Regulierung der Chloreinleitungsgeschwindigkeit oder die Mitverwendung von Harnstoff erforderlich sind.The invention is therefore based on the object of a simplified process for the preparation of alpha-chloro-N-monmoalkylacetoacetamides of the general formula

wherein R, alkyl radical having 1 to 3 carbon atoms, by reacting N-monoalkyl-acetoacetamides of the general formula

where R, which has the meaning given, is to be made available with chlorine in the presence of water-containing solvents at temperatures below 0 ° C., which guarantees a high selectivity of at least 97% with a conversion of at least 95%, without the need for expensive measures, such as the activation of an additional distillation stage to remove solvent, the regulation of the rate of chlorine introduction or the use of urea.

This object is achieved according to the invention in that N-monoalkyl-acetoacetamides and chlorine are used in a molar ratio of 1: 0.8 to 0.95, only water is used as the reaction medium and the reaction in the liquid phase at temperatures in the range from -1 ° C. to -25 ° C in the presence of an inorganic salt, which is added to the starting mixture in the amount necessary for lowering the freezing point to the reaction temperature, the use of urea being excluded.

In the process according to the invention, the N-monoalkylacetoacetamides can be used as starting products either in pure form or in the form of concentrated aqueous solutions.

Examples of N-monoalkylacetoacetamides are N-methyl, N-ethyl, N-isopropyl and N-n-propylacetoacetamides, with N-methyl and N-ethyl acetoamide being preferred.

The reactants, that is N-monoalkylacetoacetamides and chlorine, are by definition used in a molar ratio of 1: 0.8 to 0.95, preferably up to 0.90. An excess of chlorine should be avoided as this will already have a negative effect on the selectivity.

The process according to the invention can be carried out discontinuously or continuously at temperatures in the range from -1 ° C to -25 ° C, temperatures in the range from -18 ° C to -23 ° C having proven particularly useful.

The decisive measure when carrying out the process according to the invention is that only water is used as the reaction medium. To ensure that the reaction also takes place in the lower temperature range in the liquid phase, the amount of an inorganic salt required to lower the freezing point to the reaction temperature is added to the starting mixture, the chlorides of sodium, calcium and / or magnesium having proven particularly useful. However, it is also possible to use other inorganic salts which are inert towards the reactants, such as KH ₂ P0 ₄ or K ₂ HP0 ₄ . In addition, good mixing of the reactants can be ensured by mechanical movement.

The amount of water required to carry out the process according to the invention can be varied within a wide range depending on the solubility of the reactants and the inorganic salt additives present in the reaction. However, at least 0.5 part by weight of water is necessary per part by weight of acetoacetamide used. However, up to 15 parts by weight of water per part by weight of acetoacetamide can also be used. Process-technical reasons are decisive for the upper limit, since it is known that a small reaction volume is advantageous in order to achieve a good space / time yield. Preferably 0.7 to 7 parts by weight of water are used per part by weight of acetoacetamide.

After the chlorination has ended, the reaction mixture is worked up in a known manner, that is, the reaction products are separated from the aqueous phase by extraction with a water-immiscible organic solvent, such as benzene, toluene or chloroform. A neutralization of the organic phase is not necessary here, but this can be processed further without additional measures, that is, after the extractant and the hydrogen chloride formed during the chlorination have been distilled off, the desired alpha-chloroacetoacetamide remains as a residue.

However, neutralization of the aqueous phase is only necessary if the process is carried out continuously and the aqueous phase is used again as a reaction medium for the chlorination, that is to say is circulated, since hydrogen chloride dissolved therein interferes with the selectivity during the renewed chlorination. In this case, it is advantageous to carry out the neutralization with aqueous sodium hydroxide solution, since this forms the amount of sodium chloride required to lower the freezing point of the reaction medium, which further simplifies the procedure.

According to the process according to the invention, alpha-chloro-monoalkylacetoacetamides with a selectivity of up to 99.5% with a conversion of over 95.5% and in a yield of up to 95.5% of theory, based on converted mono-N- alkylacetoacetamide are produced, which was not possible by the previously known methods. This result must be rated as surprising, particularly in view of the fact that it has previously been assumed that increasing the amount of water in a reaction medium containing alkanol results in a reduction in selectivity and conversion.

example 1

The apparatus used for the chlorination consisted of an enamelled reaction stirrer with an inlet tube, cooling jacket and bottom outlet, which was connected to a sight glass to separate the layers.

• 773 Tl. Wasser,
• 227 Gew.-TI. NaCl, techn. rein, und
• 115,7 Gew.-TI. N-Methyl-acetoacetamid (MMAA), 99,5%-ig beschickt.

The reaction stirrer was in the order given

• 773 parts of water,
• 227 parts by weight NaCl, technical in, and
• 115.7 parts by weight N-methyl-acetoacetamide (MMAA), 99.5% charged.

In this mixture, a total of 56.7 parts by weight were stirred with stirring at -19 ° C to -22 ° C over 1 hour. gaseous chlorine is introduced by immersion.

• 97,4 Gew.% N-Methyl-a-chloracetoacetamid (MMCAA)
• 2,0 Gew.% N-Methylacetoacetamid (MMAA)
• 0,6 Gew.% N-Methyl-a-a-dichloracetoacetamid (MMDCAA).

The reaction mixture obtained was then exhaustively extracted at room temperature with benzene, the benzene phase was worked up by distillation and the aqueous phase was neutralized with 50% sodium hydroxide solution at room temperature. When the benzene phase was worked up by distillation, the benzene was virtually completely removed by simply stripping it off in vacuo (approx. 560 mbar, only at the end of the process the vacuum was increased to 6.5 mbar), a bottom temperature of 85 ° C. not being exceeded has been. A melt which solidified at 78 ° C. was obtained as the residue, with the following composition:

• 97.4% by weight of N-methyl-a-chloroacetoacetamide (MMCAA)
• 2.0% by weight N-methylacetoacetamide (MMAA)
• 0.6% by weight N-methyl-aa-dichloroacetoacetamide (MMDCAA).

The neutral, NaCI-containing, aqueous phase with a residual MMAA content of 21.6% by weight. was again placed in the reaction stirrer, with 50 parts of water and 94.0 parts by weight. 99.5% N-methylacetoacetamide added and chlorinated and worked up as described above.

In total, the aqueous phase was fed to chlorination 5 times. A total of 492 parts by weight. N-methylacetoacetamide (MMAA) 99.5% and 283.5% by weight. Chlorine used and a total of 588.6 parts by weight. Obtained 97.4% N-methyl-a-chloroacetoacetamide (MMCAA), that is 96.8% of theory based on implemented MMAA.

The MMCAA still has 11.8 parts by weight. MMAA included. The MMAA conversion was 95.6% and the selectivity 99.5%. Practically the same results were obtained if instead of NaCl 203 parts by weight. CaC1 ₂ or 163 parts by weight MgCl _{2 were} used.

Example 2 with 3

The procedure according to Example 1 was repeated, but with a change in the chlorine: MMAA molar ratio. The results are summarized in Table I below:

Example 4

The procedure according to Example 1 was repeated, but with the modification that instead of 99.5% N-methylacetoacetamide, an aqueous 68.7% solution was used, which was prepared by reacting diketene with aqueous 40% methylamine had been.

A total of 712 parts by weight. a 68.7% strength N-methylacetoacetamide solution (MMAA) and 580.5 parts by weight. N-Methyl-a-chloroacetoacetamide (MMCAA) of the same composition as described in Example 1 was obtained. That is 95.5% of theory based on implemented MMAA.

Example 5

The process according to Example 1 was repeated, but with the modification that after the chlorination had ended, the reaction mixture was cooled and the suspension was filtered, the resulting solid was extracted with benzene and the extract was further treated as indicated in Example 1. The residue was 309.4 parts by weight. a melt solidifying at 80 ° C., which was pure 99.5% N-methyl-2-chloroacetoacetamide (MMCAA), that is 52% of theory based on converted MMAA. The remaining mother liquor was worked up as described in Example 1, and from it a further 260 parts by weight. MMCAA 100% calculated, received.

Claims (4)

1. Process for the manufacture of alpha-chlor-N-monoalkylacetoacetamides of the general formula

in which R₁ represents alkyl radicals having from 1 to 3 carbon atoms, by reacting N-monoalkyl-acetoacetamides of the general formula

in which R, has the meaning given above, with chlorine in the presence of water-containing solvents at temperatures below 0°C, characterized in that N-monoalkyl-acetoacetamides and chlorine are used in the molar ratio of 1:0.8 to 0.95, that exclusively water is used as reaction medium and the reaction is carried out in the liquid phase at temperatures in the range of from -1°C to -25°C in the presence of an inorganic salt, that is added to the starting mixture in the amount required to reduce the freezing point to the reaction temperature, the concomitant use of urea being excluded.

2. Process according to claim 1, characterized in that N-monoalkyl-acetoacetamides and chlorine are used in the molar ratio of 1:0.8 to 0.9.

3. Process according to claim 1, characterized in that chlorides of sodium, clacium and/or magnesium are used as inorganic salts.

4. Process according to claim 1, charcterized in that 0.7 to 7 parts by weight of water are used per part by weight of acetoacetamide.